Background: As paediatric antiretroviral therapy (ART) is rapidly scaled up in Southern Africa, Human Immunodeficiency Virus (HIV) infection is becoming a chronic illness. Children growing up with HIV may begin to encounter disabilities. The relationship between HIV, disability and the need for rehabilitation has added an additional element that needs to be addressed by paediatric HIV treatment programmes. Study Objectives: 1) Estimate the prevalence of disabilities in HIV-infected and HIV-uninfected children in Lilongwe, Malawi. 2) Examine types of disability and associated clinical and socio-demographic factors. 3) Identify needs, opportunities and barriers for rehabilitation in Malawi. Methods: A case-controlled study of 296 HIV-infected children aged 2–9 years attending an ART centre in Lilongwe (cases) and their uninfected siblings (controls) was conducted. Disability was assessed using the WHO Ten Question Screen (TQS). Socio-demographic and clinical data were collected using a parent-proxy questionnaire and medical records. Results: Of 296 case and control pairs recruited, 33% (98) versus 7% (20) screened positive for a disability (OR 8.4, 4.4–15.7) respectively. Of these 98 HIV-infected cases, 6%, 36%, 33%, 53%, 46% and 6% had a vision, hearing; physical, learning/comprehension, speech or seizure-related disability respectively and 51% had multiple coexisting disabilities. HIV-infected cases with a disability were more likely to be WHO stage III or IV at enrolment (71% vs. 52%, OR 2.7, 1.5–4.2), to have had TB (58% vs. 39%, OR 2.3, 1.4–3.8) and to have below-average school grades (18% vs. 2%, OR 11.1, 2.2–54.6) than those without. Sixty-seven percent of cases with a disability had never attended any rehabilitative service. Twenty-nine percent of caregivers reported facing stigma and discrimination because of the child’s disability. Conclusion: This study reveals the magnitude of disability among HIV-infected children and the large unmet need for rehabilitation services. This expanding issue demands further investigation to provide an evidence base for holistic care for disabled children living with HIV.